Squalamine solid forms and methods of making the same

1. An isolated squalamine phosphate solid form designated as Form 2, which is at least 95% purified and having the following:

(a) an X-ray powder diffraction pattern comprising a peak, in terms of 2-theta, at about 15.2° and at about 22.9°;

(b) an X-ray powder diffraction pattern as shown in FIG. 15 with ±0.2°;

(c) a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak at about 90.9° C.;

(d) a differential scanning calorimetry (DSC) thermogram as shown in FIG. 16 with ±0.4° C.;

(e) a thermogravimetric analysis (TGA) as shown in FIG. 17 with ±0.4% weight; and/or

an X-ray powder diffraction pattern comprising the following peaks: at about 11.4° 2-theta, at about 15.2° 2-theta and at about 22.9° 2-theta, as determined on a diffractometer using Cu-Kα radiation at a wavelength of 1.5406 Å.

2. The squalamine phosphate solid form of claim 1 having:

(a) a water content of about 9-12%; or

(b) a water content of more than about 9%.

3. A pharmaceutical composition comprising the solid form of squalamine phosphate designated as Form 2 according to claim 1 and a pharmaceutically acceptable carrier.

4. The pharmaceutical composition of claim 3 , comprising at least about 90% by weight of the solid form of squalamine phosphate designated as Form 2.

5. The pharmaceutical composition of claim 3 , additionally comprising a solid form of squalamine phosphate designated as Form 1.

6. A process for preparing the squalamine phosphate solid form of claim 1 , the process comprising:

(a) dissolving squalamine lactate in base, water, and alcohol to form a first solution;

(b) heating the first solution to a first elevated temperature, wherein the first elevated temperature is greater than 25° C.;

(c) adding a first amount of phosphoric acid (H 3 PO 4 ) to the first solution to form a second solution;

(d) heating the second solution to a second elevated temperature higher than the first elevated temperature;

(e) adding a second amount of H 3 PO 4 to the second solution;

(f) obtaining a slurry; and

(g) isolating the squalamine phosphate solid form.

7. The process of claim 6 , comprising one or more of the following:

(a) the base is sodium hydroxide;

(b) the alcohol is ethanol;

(c) the first elevated temperature is at least about 35° C.;

(d) the second elevated temperature is at least about 45° C.;

(e) the step of obtaining the slurry comprises seeding the mixture with Form 1 seeds;

(f) the step of obtaining the slurry comprises adding a third amount of H 3 PO 4 to the second solution;

(g) the step of obtaining the slurry comprises cooling the second solution;

(h) the process further comprises aging the slurry prior to the isolating step; and/or

(i) the isolating step comprises filtering the slurry and washing filtered solids with acetone.

8. A squalamine phosphate solid form designated as Form 2 prepared by the process of claim 7 , wherein the squalamine phosphate solid form is at least 95% purified and have:

(a) an X-ray powder diffraction pattern comprising a peak, in terms of 2-theta, at about 15.2° and at about 22.9°;

(b) an X-ray powder diffraction pattern as shown in FIG. 15 with ±0.2°;

(c) a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak at about 90.9° C.;

(d) a differential scanning calorimetry (DSC) thermogram as shown in FIG. 16 with ±0.4° C.; and/or

(e) a thermogravimetric analysis (TGA) as shown in FIG. 17 with ±0.4% weight.